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The Journal of Neuroscience, September 1, 2000, 20(17):6459-6472

Impaired Synaptic Plasticity and cAMP Response Element-Binding Protein Activation in Ca2+/Calmodulin-Dependent Protein Kinase Type IV/Gr-Deficient Mice

Nga Ho1, Jason A. Liauw2, Frank Blaeser1, Feng Wei2, Silva Hanissian7, Lisa M. Muglia1, David F. Wozniak3, Anthony Nardi3, Kara L. Arvin1, David M. Holtzman4, David J. Linden8, Min Zhuo2, Louis J. Muglia1, 5, and Talal A. Chatila1, 6

Departments of 1 Pediatrics, 2 Anesthesiology, Anatomy and Neurobiology, 3 Psychiatry, 4 Neurology, and the Center for the Study of Nervous System Injury, 5 Molecular Biology and Pharmacology and Obstetrics and Gynecology, and 6 Pathology and Immunology, and the Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, 7 Division of Immunology/Rheumatology, The Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, and 8 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

The Ca2+/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key effector of neuronal Ca2+ signaling; its function was analyzed by targeted gene disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neuronal cAMP-responsive element binding protein (CREB) phosphorylation and Ca2+/CREB-dependent gene expression. They were also deficient in two forms of synaptic plasticity: long-term potentiation (LTP) in hippocampal CA1 neurons and a late phase of long-term depression in cerebellar Purkinje neurons. However, despite impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious deficits in spatial learning and memory. These results support an important role for CaMKIV/Gr in Ca2+-regulated neuronal gene transcription and synaptic plasticity and suggest that the contribution of other signaling pathways may spare spatial memory of CaMKIV/Gr-deficient mice.

Key words: calcium/calmodulin-dependent kinase; synaptic plasticity; LTP; LTD; CREB; memory

Copyright © 2000 Society for Neuroscience  0270-6474/00/20176459-14$05.00/0


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